Dual-action steroid derivatives with anti-inflammatory and antioxidant potency: An in vitro study

Abstract

In a recent study, we obtained two novel cortisone-derived molecules: 1,9β,17,21- tetrahydroxy-4-methyl-19-nor-9β-pregna-1,3,5(10)-trien-11,20-dione(SCA)and 1,9β,17,20β,21-pentahydroxy-4-methyl-19-nor-9β-pregna-1,3,5(10)-trien-11-one(SCB). These compounds showed a dual activity combining potent anti-inflammatory and antioxidant properties, suggesting their potential as therapeutic agents for conditions characterized by inflammation and oxidative stress, such as severe ocular disorders. In this study, in vitro experiments using human ARPE-19 and mouse 661 W cell lines, which model the retinal pigment epithelium and retinal photoreceptors respectively, revealed that pretreatment with SCA and SCB under oxidative stress with H₂O₂ preserved cell viability, reduced intracellular ROS levels, maintained tight junction integrity and Trans Epithelial Electrical Resistance (TEER). Moreover, both compounds enhanced mitochondrial respiration, thereby improving cellular bioenergetics. These results indicate that SCA and SCB could provide an effective alternative to traditional corticosteroids in treating complications in which oxidative stress and inflammation are combined, including diseases such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP). Preclinical studies on animal models and trials on human ocular diseases are necessary to validate these findings in vivo and explore their therapeutic potential.